Photo-activated hydrogels

ABSTRACT

Presented herein are compositions and articles including a crosslinkable polymer that produces a crosslinked polymer upon exposure to light and/or heat. In some embodiments, the compositions are used to fill fine lines and wrinkles to provide a cosmetic benefit. In other embodiments, the compositions and articles have desirable release properties for embedded materials.

SUMMARY

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This summary is not intended to identify key features ofthe claimed subject matter, nor is it intended to be used as an aid indetermining the scope of the claimed subject matter.

In one aspect, the present disclosure features a polymer of Formula (I)

wherein:

R¹, R², R³, and R⁶ are each independently selected from H and C₁₋₆alkyl;

R⁴ and R⁵ are each independently selected from H, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, and C₁₋₆ haloalkoxy;

X is a multivalent linker selected from

wherein R^(A) and R^(B) are each independently selected from H and C₁₋₆alkyl;

L¹ is each independently —C₁₋₄ alkylene-O—;

n is each independently an integer from 0 to 10,000, provided that thesum of all n in Formula (I) is not 0; and

m is 2, 3, or 4.

In another aspect, the present disclosure features a polymer of formula(II)

wherein:

R^(1A), R^(2A), R^(3A), R^(4A), R^(9A), R^(10A), R^(11A), R^(12A),R^(13A), and R^(14A) are each independently selected from H and C₁₋₆alkyl;

R^(5A), R^(6A), R^(7A) and R^(8A) are each independently selected fromH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, and C₁₋₆ haloalkoxy;

X^(A) is —[(CR^(C)R^(D))_(m1)O]_(m2)—, wherein R^(C) and R^(D) are eachindependently selected from H and C₁₋₆ alkyl;

m1 is 1, 2, 3, or 4;

m2 is an integer of from 1 to 5,000;

s is an integer of from 0 to 5,000;

t is an integer of from 0 to 5,000; and

s+t is an integer of from 1 to 10,000.

In yet another aspect, the present disclosure features a polymer havingFormula (III)

wherein

x is an integer of from 0 to 20,

y is an integer of from 1 to 50,

z is an integer of from 0 to 20, and

x+z is an integer of from 1 to 40.

In yet a further aspect, the present disclosure features a polymer ofFormula (IV)

In yet a further aspect, the present disclosure features a compositionor article including any one of the polymers above, and methods of usingthe composition or article.

DESCRIPTION OF THE DRAWINGS

The foregoing aspects and many of the attendant advantages of thisdisclosure will become more readily appreciated as the same becomebetter understood by reference to the following detailed description,when taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is a scheme showing the synthesis of an embodiment of a polymerof the present disclosure;

FIG. 2 is a scheme showing the synthesis of an embodiment of a polymerof the present disclosure;

FIG. 3 is scheme showing the synthesis of an embodiment of a polymer ofthe present disclosure; and

FIG. 4 is a photograph showing an embodiment of a crosslinkedfree-standing film of the present disclosure.

DETAILED DESCRIPTION

Polymeric compositions can be applied onto a skin portion to reduce theappearance of fine lines and wrinkles. For example, existing polymericcompositions based on siloxanes often require the mixing of twocompounds (prior-to or during application) to allow for resin- andcatalyst-based polymerization or cross-linking of the composition. Thesepolymers can fill in and level wrinkles and can provide day-longsmoothing cosmetic effect. However, because these siloxane compositionsinclude polymerized or cross-liked materials, they exhibit a peeling orflaking effect after a few hours of wear and are often difficult toremove. Thus, there is a need for polymeric materials (e.g., cosmeticfillers and covers) that have desirable cosmetic effects and that arealso easily removable. These polymeric materials have controllableproperties that are also suitable for a variety of applications, such asin medicine, industry, biotechnology, energy storage, batteries,agriculture, chemical safety, and drug delivery. The present disclosureseeks to fulfill these needs and provides further related advantages.

Disclosed herein are stimuli-responsive compositions and/or articlesthat include polymers that are activatable using a particular type ofstimulus. Also disclosed herein are methods of using the compositionsand/or articles. Such stimuli-responsive compositions and/or articlesare advantageous because their properties are controlled by the presenceor absence of the stimulus. For example, some compositions and/orarticles undergo a structural or compositional change when exposed to astimulus that initiates or promotes a chemical reaction. In exemplaryapplications of the disclosed embodiments, a composition and/or articlethat is coupled with photonic skin care devices is especiallyadvantageous, as the composition and/or article utilizes the energiesgenerated by the skin care devices (e.g., in the form of light and/orheat) to provide beneficial cosmetic effects to a skin area to which thecomposition has been applied.

In some embodiments, the stimuli-responsive composition and/or articlesof the present disclosure includes a polymer that is activatable usinglight and/or heat. When the composition and/or article is applied to abody portion (e.g., a skin portion) and exposed to light and/or heat,the polymer undergoes crosslinking to provide a crosslinked hydrophilicnetwork that is stable to peeling or flaking, but that is easily removedfrom a body portion, for example, by scrubbing or brushing in thepresence of water and a surfactant and/or an oil.

Definitions

At various places in the present specification, substituents ofcompounds of the disclosure are disclosed in groups or in ranges. It isspecifically intended that the disclosure include each and everyindividual subcombination of the members of such groups and ranges. Forexample, the term “C₁₋₆ alkyl” is specifically intended to individuallydisclose methyl, ethyl, C₃ alkyl, C₄ alkyl, C₅ alkyl, and C₆ alkyl.

It is also intended that a linking group definition encompasses bothforward and reverse directions. For example, when a variable for alinking group is —C(O)NH— (an amide), it is intended that the amideencompasses both —C(O)NH— and —NHC(O)—. As another example, when alinking group is —C(O)O— (an ester), it is intended that the esterencompasses both —C(O)O— and —OC(O)—.

It is further appreciated that certain features of the disclosure, whichare, for clarity, described in the context of separate embodiments, canalso be provided in combination in a single embodiment.

Conversely, various features of the disclosure which are, for brevity,described in the context of a single embodiment, can also be providedseparately or in any suitable subcombination.

As used herein, the expression “between XX and YY” refers to a range offrom XX to YY that includes the endpoints XX and YY.

As used herein, “polymer” refers to a chemical compound that is theresult of polymerization of two or more repeating constitutional units(e.g., five or more repeating constitutional units, 10 or more repeatingconstitutional units). As used herein, polymer includes oligomers, whichinclude from two to about 10 constitutional units.

As used herein, the term “copolymer” refers to a polymer that is theresult of polymerization of two or more different monomers. In someembodiments, the number and the nature of each constitutional unit areseparately controlled in a copolymer. In some embodiments, theconstitutional units are disposed in a purely random, an alternatingrandom, a regular alternating, a regular block, or a random blockconfiguration unless expressly stated to be otherwise. A purely randomconfiguration can, for example, be: x-x-y-z-x-y-y-z-y-z-z-z . . . ory-z-x-y-z-y-z-x-x . . . . An alternating random configuration can be:x-y-x-z-y-x-y-z-y-x-z . . . , and a regular alternating configurationcan be: x-y-z-x-y-z-x-y-z . . . . A regular block configuration has thefollowing general configuration: . . . x-x-x-y-y-y-z-z-z-x-x-x . . . ,while a random block configuration has the general configuration: . . .x-x-x-z-z-x-x-y-y-y-y-z-z-z-x-x-z-z-z- . . . .

As used herein, the term “substituted” or “substitution” is meant torefer to the replacing of a hydrogen atom with a substituent other thanH. For example, an “N-substituted piperidin-4-yl” refers to replacementof the H atom from the NH of the piperidinyl with a non-hydrogensubstituent such as, for example, alkyl.

As used herein, the term “alkyl” refers to a saturated hydrocarbon groupwhich is straight-chained (e.g., linear) or branched. Example alkylgroups include methyl (Me), ethyl (Et), propyl (e.g., n-propyl andisopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g.,n-pentyl, isopentyl, neopentyl), and the like. In some embodiments, analkyl group contains from 1 to about 30, from 1 to about 24, from 2 toabout 24, from 1 to about 20, from 2 to about 20, from 1 to about 10,from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 toabout 3 carbon atoms.

As used herein, the term “alkylene” refers to a linking alkyl group.

As used herein, “alkenyl” refers to an alkyl group having one or moredouble carbon-carbon bonds. In some embodiments, the alkenyl group islinear or branched. Example alkenyl groups include ethenyl, propenyl,and the like. In some embodiments, an alkenyl group contains from 2 toabout 30, from 2 to about 24, from 2 to about 20, from 2 to about 10,from 2 to about 8, from 2 to about 6, or from 2 to about 4 carbon atoms.

As used herein, “alkenylene” refers to a linking alkenyl group.

As used herein, “alkynyl” refers to an alkyl group having one or moretriple carbon-carbon bonds. In some embodiments, the alkynyl group islinear or branched. Example alkynyl groups include ethynyl, propynyl,and the like. In some embodiments, an alkynyl group contains from 2 toabout 30, from 2 to about 24, from 2 to about 20, from 2 to about 10,from 2 to about 8, from 2 to about 6, or from 2 to about 4 carbon atoms.

As used herein, “alkynylene” refers to a linking alkynyl group.

As used herein, “alkoxy” refers to an —O-alkyl group. Example alkoxygroups include methoxy, ethoxy, propoxy (e.g., n-propoxy andisopropoxy), t-butoxy, and the like.

As used herein, the term “vinyl moiety” refers to the functional group—CH═CH₂, which is optionally substituted.

As used herein, the term “aryl” refers to monocyclic or polycyclic(e.g., having 2, 3, or 4 fused rings) aromatic hydrocarbons such as, forexample, phenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, andindenyl. In some embodiments, aryl groups have from 6 to about 20 carbonatoms. In some embodiments, an aryl group is a 5, 6, or 7-memberedaromatic ring.

As used herein, the term “halo” or “halogen” includes fluoro, chloro,bromo, and iodo.

As used herein, the term “vinyl moiety” refers to the functional group—CH═CH₂, which is optionally substituted.

As used herein, “crosslink” refers to a bond, atom, or group of atomsthat connects two adjacent chains of atoms in a large molecule such as apolymer. Internal crosslinking between two sites on a single molecule(e.g., a polymer) is also possible.

As used herein, “hydrogel” refers a substance formed when an organichydrophilic polymer, (natural or synthetic) that is crosslinked viacovalent, ionic, or hydrogen bonds to form a three-dimensionalopen-lattice network structure that entraps water molecules to form agel. In some embodiments, hydrogels contains 90% or more water (e.g.,80% or more, 70% or more, 60% or more, or 50% or more) by volume.

As used herein, “molecular weight” of a polymer refers to a numberaverage molecular weight (M_(n)) that is determined by titration, byvapor phase osmometry, or by gel permeation chromatography.

As used herein, the term “constitutional unit” of a polymer refers anatom or group of atoms in a polymer, including a part of the chaintogether with its pendant atoms or groups of atoms, if any. In someembodiments, the constitutional unit refers to a repeat unit. In someembodiments, the constitutional unit refers to an end group on a polymerchain. For example, in some embodiments, the constitutional unit ofpolyethylene glycol is —CH₂CH₂O— corresponding to a repeat unit, or—CH₂CH₂OH corresponding to an end group.

As used herein, the term “repeat unit” corresponds to the smallestconstitutional unit, the repetition of which constitutes a regularmacromolecule (or oligomer molecule or block).

As used herein, the term “end group” refers to a constitutional unitwith only one attachment to a polymer chain, located at the end of apolymer. For example, in some embodiments, the end group is derived froma monomer unit at the end of the polymer, once the monomer unit has beenpolymerized. As another example, the end group is a part of a chaintransfer agent or initiating agent that was used to synthesize thepolymer.

As used herein, the term “terminus” of a polymer refers to aconstitutional unit of the polymer that is positioned at the end of apolymer backbone.

As used herein, “amino acid” refers to an organic compound including aprimary or secondary amine and a carboxylic acid functional group, witha side chain. Amino acids have a molecular weight of 500 or less.Non-limiting examples of natural amino acid include histidine,isoleucine, leucine, lysine, methionine, phenylalanine, threonine,tryptophan, valine, alanine, arginine, asparagine, aspartic acid,cysteine, glutamic acid, glutamine, glycine, ornithine, proline,selenocysteine, serine, tyrosine, selenocysteine, pyrrolysine,N-formylmethionine, etc. Non-limiting examples of non-natural aminoacids include, for example, amino acid analogs such asazetidine-2-carboxylic acid, 3,4-dehydroproline, perthiaproline,canavanine, ethionine, norleucine, aminohexanoic acid, homoallylglycine,homopropargylglycine, etc. Non-limiting examples of non-natural aminoacids also include sugar amino acids such as N-methyl-glucamine whereamino and carboxyl functional groups have been incorporated into a sugarframework (e.g., at the two termini of regular 2,5 or 2,6-anhydro sugarframeworks). In some embodiments, the term “amino acid” also includes“amino acid residues,” which are amino acids that are incorporated intoa larger molecule, for example, by reaction of the amino or carboxylicacid functional groups with a reactive moiety. When the amino acid isincorporated into a larger molecule, what remains of the amino acid inthe larger molecule is generally referred to as an “amino acid residue”.For example, the amino acid residue can lack a hydrogen of the aminogroup, or a hydroxyl moiety of the carboxyl group, or both.

As used herein, “peptide” refers to a chain of amino acid monomerslinked by amide bonds. In some embodiments, a peptide includes from 2amino acid residues to 50 amino acids residues (e.g., from 2 to 20 aminoacid residues, from 2 to 10 amino acid residues, or from 5 to 10 aminoacid residues).

As used herein, “activatable” refers to a material that is capable ofundergoing a structural or conformational change upon application of astimulus. The structural or conformational change confers a change in aproperty, function, or appearance, in the material. For example, in someembodiments, a composition and/or article has a polymer that can becrosslinked when exposed to light and/or heat. When exposed to lightand/or heat, the polymer undergoes crosslinking to provide a crosslinkednetwork that can absorb water.

As used herein, the term “hydrophilic” refers to a moiety or a moleculethat is attracted to and tends to be dissolved by water. The hydrophilicmoiety is miscible with an aqueous phase. Hydrophilic molecules arepolar and/or ionizable in aqueous conditions. In some embodiments,hydrophilic molecules are ionizable under aqueous conditions and/orcontain polar functional groups such as amides, hydroxyl groups, orethylene glycol residues. Examples of hydrophilic moieties includecarboxylic acid groups, amino groups, hydroxyl groups, etc.

As used herein, the term “hydrophobic” refers to a moiety or a moleculethat is not attracted to water with significant nonpolar surface area atphysiological pH and/or salt conditions. Hydrophobic molecules ormoieties tend to be non-polar in aqueous conditions. Examples ofhydrophobic moieties include alkyl groups, aryl groups, etc.

As used herein, a “cosmetic composition” refers to a compositionsuitable for topical application on keratinous tissue.

As used herein, “keratinous tissue” refers to the keratin-containinglayers disposed as the outermost protective covering of mammals whichinclude, but are not limited to, skin, hair, nails, and cuticles.

As used herein, “effective amount” refers to an amount sufficient toinduce one or more effects to the affected area. Non-limiting examplesof effects include a change in skin appearance (e.g., decrease inwrinkles), a change in moisture retention of skin, a change in skintexture, etc.

As used herein, “improve skin condition” or “improving skin condition”includes to effecting a visually and/or tactilely perceptible positivechange, or benefit, in skin appearance and feel. Benefits that areprovided include, but are not limited to, one or more of the following:reducing the appearance of wrinkles, coarse deep lines, fine lines,crevices, bumps, and large pores; thickening of keratinous tissue (e.g.,building the epidermis and/or dermis and/or sub-dermal layers of theskin, and where applicable, the keratinous layers of the nail and hairshaft, to reduce skin, hair, or nail atrophy); increasing theconvolution of the dermal-epidermal border (also known as the reteridges); preventing loss of skin or hair elasticity, for example, due toloss, damage and/or inactivation of functional skin elastin, resultingin such conditions as elastosis, sagging, loss of skin or hair recoilfrom deformation; reduction in cellulite; change in coloration to theskin, hair, or nails, for example, under-eye circles, blotchiness (e.g.,uneven red coloration due to, for example, rosacea), sallowness, etc.

As used herein, the term “signs of skin aging” includes all outwardvisibly and tactilely perceptible manifestations, as well as any macro-or micro-effects, due to keratinous tissue aging. These signs may resultfrom processes which include, but are not limited to, the development oftextural discontinuities such as wrinkles and coarse deep wrinkles, finelines, skin lines, crevices, bumps, large pores, unevenness orroughness; loss of skin elasticity; discoloration (including undereyecircles); blotchiness; sallowness; hyperpigmented skin regions such asage spots and freckles; keratoses; abnormal differentiation;hyperkeratinization; elastosis; collagen breakdown, and otherhistological changes in the stratum corneum, dermis, epidermis, vascularsystem (e.g., telangiectasia or spider vessels), and underlying tissues(e.g., fat and/or muscle), especially those proximate to the skin.

As used herein, “cosmetically acceptable” refers to a composition and/orarticle component that is safe for contact with a human integument.

As used herein, “physiological conditions” refer to a temperature rangeof about 37 degrees Celsius and a pH of about 7 (e.g., 7.3-7.4).

As used herein, “multivalent” refers to an atom or chemical moiety thatforms bonds to two or more discrete moieties. For example, a carbon atomcan form bonds to 2, 3, or 4 moieties and can be divalent, trivalent, ortetravalent, respectively.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art. Although methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of the presentdisclosure, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

Compositions and Articles Including Crosslinkable Polymers

In some embodiments, the compositions and/or articles of the presentdisclosure include a polymer that can be crosslinked to produce acrosslinked polymer. When the composition and/or article is applied to askin portion and the polymer is crosslinked, the crosslinked polymerfills fine lines and wrinkles. The polymers are crosslinked using lightand/or heat to provide a network that has increased molecular weightcompared to the uncrosslinked polymer, the crosslinked network iscapable of absorbing water and produces a mechanical leveling andfilling effect.

The present disclosure provides, inter alia, a polymer of Formula (I)

wherein:

R¹, R², R³, and R⁶ are each independently selected from H and C₁₋₆alkyl;

R⁴ and R⁵ are each independently selected from H, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, and C₁₋₆ haloalkoxy;

X is a multivalent linker selected from

wherein R^(A) and R^(B) are each independently selected from H and C₁₋₆alkyl;

L¹ is each independently —C₁₋₄ alkylene-O—;

n is each independently an integer from 0 to 10,000, provided that thesum of all n in Formula (I) is not 0; and

m is 2, 3, or 4.

In some embodiments, R¹, R², R³, and R⁶ are each independently selectedfrom H and C₁₋₃ alkyl.

In some embodiments, R¹, R², and R³ are each independently selected fromH and C₁₋₃ alkyl.

In some embodiments, R¹, R², and R³ are each independently selected fromC₁₋₃ alkyl.

In some embodiments, R² and R³ are each H and R¹ is C₁₋₃ alkyl.

In some embodiments, R² and R³ are each H and R¹ is methyl.

In some embodiments, R¹, R², R³, and R⁶ are each H.

In some embodiments, R⁶ is H.

In some embodiments, R⁶ is C₁₋₃ alkyl.

In some embodiments, R⁴ and R⁵ are each independently selected from Hand C₁₋₆ alkyl.

In some embodiments, R⁴ and R⁵ are each independently selected from Hand C₁₋₃ alkyl.

In some embodiments, R⁴ and R⁵ are each independently H.

In some embodiments, R⁴ and R⁵ are each independently C₁₋₃ alkyl.

In some embodiments, R⁴ and R⁵ are each independently selected from Hand methyl.

In some embodiments, X is a multivalent linker selected from

In some embodiments, R^(A) and R^(B) are each H.

In some embodiments, R^(A) and R^(B) are each independently selectedfrom C₁₋₆ alkyl.

In some embodiments, R^(A) and R^(B) are each independently selectedfrom H and methyl.

In some embodiments, L¹ is each CH₂O.

In some embodiments, L¹ is each CH₂CH₂O.

In some embodiments, n is each independently an integer of from 1 to10,000.

In some embodiments, n is each independently an integer of from 2 to10,000.

In some embodiments, n is each independently an integer of from 2 to5,000.

In some embodiments, n is each independently an integer of from 2 to2,500.

In some embodiments, m is 2 (i.e., X is a divalent linker).

In some embodiments, m is 4 (i.e., X is a tetravalent linker).

In some embodiments, the polymer is a dendrimer.

This disclosure also provides, inter alia, a composition including apolymer of Formula (I).

This disclosure also provides, inter alia, an article including apolymer of Formula (I).

This disclosure also provides, inter alia, a polymer of Formula (IV)

This disclosure also provides, inter alia, a composition including apolymer of Formula (IV).

This disclosure also provides, inter alia, an article including apolymer of Formula (IV).

This disclosure also provides, inter alia, a polymer of formula (II)

wherein:

R^(1A), R^(2A), R^(3A), R^(4A), R^(9A), R^(10A), R^(11A), R^(12A),R^(13A), and R^(14A) are each independently selected from H and C₁₋₆alkyl;

R^(5A), R^(6A), R^(7A) and R^(8A) are each independently selected fromH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, and C₁₋₆ haloalkoxy;

X^(A) is —[(CR^(C)R^(D))_(m1)O]_(m2)—, wherein R^(C) and R^(D) are eachindependently selected from H and C₁₋₆ alkyl;

m1 is 1, 2, 3, or 4;

m2 is an integer of from 1 to 5000;

s is an integer of from 0 to 5000;

t is an integer of from 0 to 5000; and

s+t is an integer of from 1 to 10,000.

In some embodiments, R^(1A), R^(2A), R^(3A), R^(4A), R^(6A), R^(7A),R^(9A), R^(10A), R^(11A), R^(12A), and R^(14A) are each H.

In some embodiments, R^(2A), R^(3A), R^(11A), and R^(12A) are H andR^(1A) and R^(10A) are each C₁₋₆ alkyl.

In some embodiments, R^(2A), R^(3A), R^(11A), and R^(12A) are H andR^(1A) and R^(10A) are each methyl.

In some embodiments, R^(5A), R^(8A), and R^(13A), are each methyl.

In some embodiments, R^(6A), R^(8A), and R^(13A), are each methyl.

In some embodiments, R^(6A), R^(8A), and R^(14A) are each methyl.

In some embodiments, R^(4A) and R^(9A) are each H or methyl.

In some embodiments, R^(4A) and R^(9A) are each H.

In some embodiments, X^(A) is —CH₂CH₂O—.

In some embodiments, m2 is an integer of from 1 to 5000 (e.g., from 2 to5000).

In some embodiments, s is an integer of from 1 to 5000 (e.g., from 2 to5000).

In some embodiments, t is an integer of from 1 to 5000 (e.g., from 2 to5000).

In some embodiments, s+t is an integer of from 1 to 10,000 (e.g., from 1to 8,000, from 1 to 5,000, from 1 to 2,500, from 1 to 1,000, from 1 to500, from 1 to 100, from 1 to 10, from 3 to 8,000, from 3 to 5,000, from3 to 2,500, from 3 to 1,000, from 3 to 500, from 3 to 100, or from 3 to10,). In some embodiments, s+t is an integer of 1 or greater (e.g., 10or greater, 100 or greater, 500 or greater, 1,000 or greater, or 2,500or greater) and/or 5,000 or less (e.g., 2,500 or less, 1,000 or less,500 or less, 100 or less, or 10 or less).

In some embodiments, each of s and t are independently an integer offrom 0 to 5,000 (e.g., from 1 to 5,000, from 1 to 2,500, from 1 to1,000, from 1 to 100, from 3 to 5,000, from 3 to 2,500, from 3 to 1,000,or from 3 to 100).

In some embodiments, m2 is an integer of from 0 to 5,000 (e.g., from 1to 5,000, from 1 to 2,500, from 1 to 1,000, from 1 to 100, from 1 to 50,from 3 to 5,000, from 3 to 2,500, from 3 to 1,000, from 3 to 100, orfrom 3 to 50).

In some embodiments, s+t is an integer of from 1 to 40 (e.g., from 1 to30, from 1 to 20, from 1 to 10, from 1 to 6, from 3 to 30, from 3 to 20,from 3 to 10, or from 3 to 6). In some embodiments, s+t is an integer of1 or greater (e.g., 3 or greater, 6 or greater, 10 or greater, 20 orgreater, 30 or greater) and/or 40 or less (e.g., 30 or less, 20 or less,10 or less, 6 or less, or 3 or less).

In some embodiments, each of s and t are independently an integer offrom 0 to 20 (e.g., from 1 to 20, from 2 to 20, from 2 to 10, or from 1to 6)

In some embodiments, m2 is an integer of from 1 to 40 (e.g., from 1 to30, from 1 to 20, from 1 to 15, from 2 to 40, from 2 to 30, from 2 to20, from 2 to 15, from 9 to 40, from 9 to 30, from 9 to 20, from 9 to15, from 12 to 40, from 12 to 30, from 12 to 20, or from 12 to 15).

This disclosure also provides, inter alia, a composition including apolymer of Formula (II).

This disclosure also provides, inter alia, an article including apolymer of Formula (II).

Example 1 and FIG. 1, below, describe the synthesis and characterizationof acrylamide-terminated oligo/poly-ethylene glycol. Example 2 and FIG.2, below, describe the synthesis and characterization ofacrylamide-terminated tetravalent poly(ethylene glycol).

The present disclosure also provides, inter alia, a polymer of Formula(III):

wherein x is an integer of from 0 to 20,

y is an integer of from 1 to 50,

z is an integer of from 0 to 20, and

x+z is 1 or greater.

In some embodiments, x+z is an integer of from 1 to 40 (e.g., from 1 to30, from 1 to 20, from 1 to 10, from 1 to 6, from 3 to 30, from 3 to 20,from 3 to 10, or from 3 to 6). In some embodiments, x+z is an integer of1 or greater (e.g., 3 or greater, 6 or greater, 10 or greater, 20 orgreater, 30 or greater) and/or 40 or less (e.g., 30 or less, 20 or less,10 or less, 6 or less, or 3 or less).

In some embodiments, each of x and z are independently an integer offrom 0 to 20 (e.g., from 1 to 20, from 2 to 20, from 2 to 10, or from 1to 6)

In some embodiments y is an integer of from 1 to 40 (e.g., from 1 to 30,from 1 to 20, from 1 to 15, from 2 to 40, from 2 to 30, from 2 to 20,from 2 to 15, from 9 to 40, from 9 to 30, from 9 to 20, from 9 to 15,from 12 to 40, from 12 to 30, from 12 to 20, or from 12 to 15).

In some embodiments, the present disclosure provides a compositionincluding a polymer of Formula (III).

This disclosure also provides, inter alia, an article including apolymer of Formula (II).

Example 3 and FIG. 3, below, describe the synthesis and characterizationof acrylamide-terminated Jeffamine®.

In some embodiments, the polymer of Formula (I), Formula (II), orFormula (III) is crosslinked in the presence of a free-radical initiatorand light and/or heat. In some embodiments, the light includes awavelength of between 200 and 1300 nm (e.g., between 280 and 900 nm,between 280 and 700 nm, between 280 and 500 nm, between 280 and 450 nm,between 280 and 400 nm, between 280 and 350 nm, or between 300 and 450).In some embodiments, the polymer of Formula (I), Formula (II), orFormula (III) is crosslinkable in the presence of a free-radicalinitiator and heat. Polymerization of polymers using light and/or heatand a radical initiator is described, for example, in Odian, George G.Principles of Polymerization, 4^(th) ed., Hoboken, N.J.:Wiley-Interscience, 2004, herein incorporated by reference in itsentirety.

When the polymer of Formulas (I), (II), or (III) is crosslinked, thevinyl moieties at the termini of the polymers crosslink with one anothervia radical-initiated polymerization to form alkylene linkages asdescribed, for example, in Odian, George G. Principles ofPolymerization, 4^(th) ed., Hoboken, N.J.: Wiley-Interscience, 2004,herein incorporated by reference in its entirety. In some embodiments,when the polymer is crosslinked, the polymer forms a film. In someembodiments, when the polymer is crosslinked, the crosslinked polymer isresistant to a water rinse at 50 psi or more (e.g., 40 psi or more, 30psi or more, or 20 psi or more) and/or 55 psi or less (e.g., 50 psi orless, 40 psi or less, 30 psi or less, or 20 psi or less). In someembodiments, when the polymer is crosslinked, the crosslinked polymerhas an elastic modulus that increases by 10% or more (e.g., 50% or more,100% or more, 200% or more, 300% or more, or 400% or more) and/or 500%or less (e.g., 400% or less, 300% or less, 200% or less, 100% or less,or 50% or less) compared to an uncrosslinked polymer. In someembodiments, when the polymer is crosslinked, the polymer forms ahydrogel. In some embodiments, the hydrogel is in the form of a film. Inan embodiment, hydrogel is in the form of a surface-attached hydrogelfilm. In some embodiments, the hydrogel absorbs up to 50% by volume ofwater. In some embodiments, the hydrogel absorbs water to provide ahydrogel having a water content of 75% or more (e.g., 80% or more, 85%or more, 90% or more, or 95% or more) by weight.

Composition and articles including crosslinkable polymers are alsodescribed, for example, in U.S. patent application Ser. No.14/582,824,entitled “Photo-Activated Hydrogels”, filed Dec. 24, 2014,herein incorporated by reference in its entirety.

The composition and/or article that includes the crosslinked polymer canbe easily removed from a bodily portion to which the composition and/orarticle has been applied by scrubbing with an oscillating brush deviceusing water and a surfactant. In an embodiment, a hydrogel film can bepeeled off a surface.

As discussed above, this disclosure provides articles and compositionsincluding a polymer of Formulae (I), (II), or (III). Examples ofarticles include medical devices, such as bandages, dressing, tissuescaffolds, cardiovascular devices (e.g., stents, endoprostheses,implants, lenses, medical films, etc.) In some embodiments, the polymerforms a portion of the article, such as a lining in a bandage or adressing, or a coating on a medical device. In certain embodiments, thepolymer forms the entirety of the article, such as a tissue scaffold.

In some embodiments, a composition and/or article that includes apolymer of Formulae (I), (II), or (III) is in the form of a blend thatincludes non-crosslinkable components (e.g., PEG, pigments, therapeuticagents, etc.) dispersed or otherwise contained within the blend. Whenthe polymer of Formulae (I), (II), or (III) is crosslinked, the polymerforms a network that contains the non-crosslinkable components, wherethe non-crosslinkable components are enmeshed within the crosslinkedpolymeric network. Example 4, below, describes the crosslinking ofacrylamide-functionalized polyethylene glycol in a blend.

In some embodiments, a composition that includes a polymer of Formula(I), Formula (II), or Formula (III) is a cosmetic composition. In someembodiments, the cosmetic composition is a homogeneous mixture. In someembodiments, the cosmetic composition is a cream, a powder, or a lotion.

In some embodiments, the composition is a skin humectant. In someembodiments, the composition further includes a colorant, for example,titanium oxide and/or iron oxide. Example 5, below, describes apigmented photo-crosslinked hydrogel.

In some embodiments, the composition further includes a carrier (e.g., alipophilic carrier such as mineral oil, oleic acid, etc.). In someembodiments, the cosmetic composition is a foundation, a blush, ahighlighter, or a bronzer.

In some embodiments, the composition and/or article further includes aradical initiator, such as anthraquinone-2-sulfonic acid sodium salt or4,4-azobis(4-cyanovaleric acid), in an amount sufficient to initiate areaction. In some embodiments, the radical initiator is present in acomposition and/or article in and amount of 0.01% or more (e.g., 0.05%or more, 0.1% or more, 0.3% or more, 0.5% or more, or 0.7% or more)and/or 1% or less (e.g., 0.7% or less, 0.5% or less, 0.3% or less, 0.1%or less, 0.05% or less) by mass.

Additional Components

In some embodiments, in addition to the polymers above, the compositionand/or article includes any number of additional components, such as,but not limited to: active ingredients (e.g., cosmetic, dermatological,and/or pharmaceutical), alcohols, allergy inhibitors, amino acids,anti-acne agents (e.g., salicylic acid), anti-aging agents, antiseptics,antifungal agents, antiperspirants, analgesics, anti-hair loss agents,anti-wrinkle agents, antibacterial agents, anti-microbial agents,anti-oxidants, anti-inflammatory agents, burn healing agents, colorants(e.g., lakes, pigments, and the like), de-pigmentation agents,deodorants, dyes, emollient (e.g., glycerin, butylene glycol),excipients, fatty substances, fillers, film formers (e.g., dimethiconeacrylate copolymer, ethylhexyl acrylate copolymer), fragrances, freeradical scavengers, glycerin, glycerin monostearate, glycerindistearate, hair growth agents, hair conditioners, hair softeners, hairmoisturizers, herbal extracts, humectants (e.g., hyaluronic acid, oroticacid, lipoprotein), insect repellants, medication, moisturizers,non-active carrier oils (e.g., triglycerides, silicone oils, mineraloils), oils, peptides, polypeptides, proteins, perfumes, pigments,preservatives, plasticizers, reflectants, sebum absorbers, skinlightening agents, sunscreens, surfactants, tanning agents, thickeningagents (e.g., hydroxyethylcellulose, xanthan gum, carbomer), Vaseline,vasoconstrictors, vasodilators, vitamins (e.g., Vitamin A, Vitamin E),water, waxes, and/or combinations thereof.

In some embodiments, the composition and/or article includes otheringredients (e.g., cosmetic ingredients) such as, but not limited to,humectants, emollients, moisturizers, anti-wrinkle ingredients,concealers, matte finishing agents, pigments, colorants, proteins,anti-oxidants, bronzers, chelating agents, emulsifiers, ultraviolet (UV)absorbing agents, oil absorbing agents, anti-foam agents, anti-tackagents, thickeners, fragrances, preservatives, anti-microbials,fungistats, neutralizing agents, vitamins, plasticizers, cohesionagents, basifying and acidifying agents, fillers, solvents, and/ormixtures thereof.

In some embodiments, the composition and/or article contains additionalingredients such as alkalinizing agents, emulsifying agents, emollients,plasticizers, preservatives, humectants, moisturizing agents, solvents,tonicity agents, active ingredients suitable to provide anti-agingbenefits, and/or mixtures thereof. Examples of preferred additionalingredients include glycerin.

In some embodiments, additional ingredients are added to thecompositions and/or articles as detailed below.

Colorants or pigments: n some embodiments, the composition and/orarticle includes one or more powders (e.g., cosmetic powders), forexample, calcium aluminum borosilicate, PMMA, polyethylene, polystyrene,methyl methacrylate crosspolymer, nylon-12, ethylene/acrylic acidcopolymer, boron nitride, Teflon, silica, or the like. In someembodiments, the composition and/or article includes colorants orpigments to impart a desired color or effect, examples are inorganicpigments, organic pigments, and/or lakes. Exemplary inorganic pigmentsinclude, but are not limited to, metal oxides and metal hydroxides suchas magnesium oxide, magnesium hydroxide, calcium oxide, calciumhydroxides, aluminum oxide, aluminum hydroxide, iron oxides (α-Fe₂O₃,γ-Fe₂O₃, Fe₃O₄, FeO), red iron oxide, yellow iron oxide, black ironoxide, iron hydroxides, titanium dioxide, titanium lower oxides,zirconium oxides, chromium oxides, chromium hydroxides, manganeseoxides, cobalt oxides, cerium oxides, nickel oxides and zinc oxides andcomposite oxides and composite hydroxides such as iron titanate, cobalttitanate and cobalt aluminate. Suitable inorganic pigments also includenon-metal oxides such as alumina and silica, ultramarine blue (i.e.,sodium aluminum silicate containing sulfur), Prussian blue, manganeseviolet, bismuth oxychloride, talc, mica, sericite, magnesium carbonate,calcium carbonate, magnesium silicate, aluminum magnesium silicate,silica, titanated mica, iron oxide titanated mica, bismuth oxychloride,and the like. Organic pigments include, but are not limited to, at leastone of carbon black, carmine, phthalocyanine blue and green pigment,diarylide yellow and orange pigments, and azo-type red and yellowpigments such as toluidine red, litho red, naphthol red and brownpigments, and combinations thereof.

“Lakes” generally refer to a colorant prepared from a water-solubleorganic dye, (e.g., D&C or FD&C) which has been precipitated onto aninsoluble reactive or adsorptive substrate or diluent. The term “D&C” asused herein means drug and cosmetic colorants that are approved for usein drugs and cosmetics by the FDA. The term “FD&C” as used herein meansfood, drug, and cosmetic colorants which are approved for use in foods,drugs, and cosmetics by the FDA. Certified D&C and FD&C colorants arelisted in 21 C.F.R. §74.101 et seq. and include the FD&C colors Blue 1,Blue 2, Green 3, Orange B, Citrus Red 2, Red 3, Red 4, Red 40, Yellow 5,Yellow 6, Blue 1, Blue 2, Orange B, Citrus Red 2, and the D&C colorsBlue 4, Blue 9, Green 5, Green 6, Green 8, Orange 4, Orange 5, Orange10, Orange 11, Red 6, Red 7, Red 17, Red 21, Red 22, Red 27, Red 28, Red30, Red 31, Red 33, Red 34, Red 36, Red 39, Violet 2, Yellow 7, Yellow8, Yellow 10, Yellow 11, Blue 4, Blue 6, Green 5, Green 6, Green 8,Orange 4, Orange 5, Orange 10, Orange 11, and so on. Substrates suitablefor forming lakes include, without limitation, mica, bismuthoxychloride, sericite, alumina, aluminum, copper, bronze, silver,calcium, zirconium, barium, and strontium, titanated mica, fumed silica,spherical silica, polymethylmethacrylate (PMMA), micronized teflon,boron nitride, acrylate copolymers, aluminum silicate, aluminum starchoctenylsuccinate, bentonite, calcium silicate, cellulose, chalk, cornstarch, diatomaceous earth, fuller's earth, glyceryl starch, hectorite,hydrated silica, kaolin, magnesium aluminum silicate, magnesiumtrisilicate, maltodextrin, montmorillonite, microcrystalline cellulose,rice starch, silica, talc, mica, titanium dioxide, zinc laurate, zincmyristate, zinc rosinate, alumina, attapulgite, calcium carbonate,calcium silicate, dextran, nylon, silica silylate, silk powder,sericite, soy flour, tin oxide, titanium hydroxide, trimagnesiumphosphate, walnut shell powder, and mixtures thereof. Suitable lakesinclude, without limitation, those of red dyes from the monoazo, disazo,fluoran, xanthene, or indigoid families, such as Red 4, 6, 7, 17, 21,22, 27, 28, 30, 31, 33, 34, 36, and Red 40; lakes of yellow pyrazole,monoazo, fluoran, xanthene, quinoline, dyes or salt thereof, such asYellow 5, 6, 7, 8, 10, and 11; lakes of violet dyes including those fromthe anthroquinone family, such as Violet 2, as well as lakes of orangedyes, including Orange 4, 5, 10, 11, and the like. Suitable lakes of D&Cand FD&C dyes are defined in 21 C.F.R. §82.51.

In some embodiments, the coloring agents are surface treated, forexample, to make the coloring agents more hydrophobic or moredispersible in a vehicle. In one embodiment, the surface of the coloringagents is, for example, covalently or ionically bound to an organicmolecule or silicon-based molecule or is adsorbed thereto, or thecoloring agents is physically coated with a layer of material. Incertain embodiments, the surface treatment compound is attached to thecoloring agents through any suitable coupling agent, linker group, orfunctional group (e.g., silane, ester, ether, etc). In some embodiments,the compound includes a hydrophobic portion which is selected from, forexample, alkyl, aryl, allyl, vinyl, alkyl-aryl, aryl-alkyl,organosilicone, di-organosilicone, dimethicones, methicones,polyurethanes, silicone-polyurethanes, and fluoro- orperfluoro-derivatives thereof. Other hydrophobic modifiers includelauroyl lysine, isopropyl titanium triisostearate (ITT), ITT anddimethicone (ITT/dimethicone) cross-polymers, ITT and amino acid,ITT/triethoxycaprylylsilane crosspolymer, waxes (e.g., carnauba), fattyacids (e.g., stearates), HDI/trimethylol hexylactone crosspolymer, PEG-8methyl ether triethoxysilane, aloe, jojoba ester, lecithin,perfluoroalcohol phosphate, and Magnesium Myristate (MM), to name a few.

In some embodiments, a pigment component includes an alkyl silanesurface-treated colorant including an alumina substrate (e.g., plateletshaped) and a pigment, dye, or lake bonded to the alumina substrate byan alkyl silane surface treatment. In some embodiments, the alkyl silaneis octylsilane, and is formed by treatment with triethoxycaprylylsilane. Non-limiting examples of such colorants include, but arenot limited to, alumina/titanium dioxide/triethoxycaprylylsilane 1%(COVALUMINE™ Atlas White AS), alumina/D&C Red aluminum lakeCTD/Triethoxycaprylylsilane 1% (COVALUMINE™ Red Rose AS), alumina/D&Cred aluminum lake CTD/triethoxycaprylylsilane 1% (COVALUMINE™ Sonoma RedAS), alumina/black iron oxide CTD/triethoxycaprylylsilane 1%(COVALUMINE™ Sonoma Black AS), alumina/D&C red #6 aluminum lakeCTD/triethoxycaprylylsilane 1% (COVALUMINE™ Fire Red AS), alumina/yellowiron oxide CTD/triethoxycaprylylsilane 1% (COVALUMINE™ sonoma yellowAS), alumina/D&C blue #1 aluminum lake CTD/triethoxycaprylylsilane 1%(COVALUMINE™ Astral Blue AS), alumina/carmineCTD/triethoxycaprylylsilane 1% (COVALUMINE™ Campari AS), alumina/yellow#5 CTD/triethoxycaprylylsilane 1% (COVALUMINE™ Sunburst AS),alumina/triethoxycaprylylsilane 1%, and combinations thereof, each ofwhich is available from SENSIENT™ CosmeticTechnologies LCW.

In some embodiments, interference or pearl pigments are included in thecomposition and/or article. Interference or pearl pigments typically areformed of micas layered with about 50 to 300 nm films of TiO₂, Fe₂O₃, orCr₂O₃ or the like. These include white nacreous materials, such as micacovered with titanium oxide or covered with bismuth oxychloride; andcolored nacreous materials, such as titanium mica with iron oxides,titanium mica with ferric blue or chromium oxide, titanium mica with anorganic pigment of the aforementioned type. In some embodiments,interference or pearl pigments are used collectively in an amount ofless than 1.0 wt %. In some embodiments, the pearlescent component has abismuth oxychloride based pearlescent ingredient or reflectance pearls.It is believed that bismuth oxychloride matches the skin's naturalpearlescence more than compounds such as titanium oxide. However, otherpearlescent ingredients may be used. In some embodiments, thepearlescent component is CHROMA-LITE, which is a combination of coloredpigment bonded to BI-LITE 20 (bismuth oxychloride and mica) usingcalcium stearate.

In some embodiments, the composition and/or article includescosmetically or pharmaceutically acceptable vehicles. In someembodiments, the vehicle includes a liquid, including a single phase, adual-phase system, or an emulsion. Emulsions include oil-in-water,silicone-in-water, water-in-oil, water-in-silicone, and the like. Whenformulated as an emulsion, an emulsifier is typically included. Examplesof cosmetically or pharmaceutically acceptable vehicles include volatilesilicones (e.g., cyclopentasiloxane), hydrocarbons, ester oils, loweralcohols (e.g., ethanol, isopropyl alcohol, etc.), and water.

In some embodiments, the composition and/or article includes emollients.Examples of emollients include, but are not limited to, esters oils(e.g., the etherification product of an acid of the form R^(A)(COOH)₁₋₂with an alcohol of the form R^(B)(OH)₁₋₃ where R^(A) and R^(B) are eachindependently linear, branched, or cyclic hydrocarbon groups, optionallycontaining unsaturated bonds, and having from 1 to 30 carbon atoms,preferably from 2 to 30 carbon atoms, and more preferably, from 3 to 30carbon atoms, optionally substituted with one or more functionalitiesincluding hydroxyl, oxa, oxo, and the like. In some embodiments, atleast one of R^(A) and R^(B) includes at least one aliphatic chain. Theesters defined above include, without limitation, the esters ofmono-acids with mono-alcohols, mono-acids with diols and triols,di-acids with mono-alcohols, and tri-acids with mono-alcohols. Otheremollients include dimethicone. In some embodiments, humectants, such asglycerin and other C1-10 polyols or diols are also included.

In some embodiments, the composition and/or article includes fillers inan amount from about 1% to about 20% (e.g., from about 1% to about 10%)by weight of the final composition. Examples of fillers include, but arenot limited to, silica, PMMA, nylon, alumina, barium sulfate, or anyother filler typically used in such compositions.

In some embodiments, the composition and/or article includes filmformers. Examples of polymeric film formers include cellulosics,polyolefins, polyvinyls, polacrylates, polyurethanes, silicones,silicone acrylates, polyamides, polyesters, fluoropolymers, polyethers,polyacetates, polycarbonates, polyimides, rubbers, epoxies, formaldehyderesins, and homopolymers and copolymers of any of the foregoing.

In some embodiments, the composition and/or article includes oils.Suitable non-limiting examples of oils for the oil phase (for example,in an emulsion) include natural and synthetic oils, including animal,vegetable, and petroleum oils; fatty acid triglycerides; fatty acidesters such as octyl palmitate, isopropyl myristate and isopropylpalmitate; ethers such as dicapryl ether; fatty alcohols such as cetylalcohol, stearyl alcohol and behenyl alcohol; sterols; hydrocarbons suchas isooctane, isododecane, isohexadecane, decane, dodecane, tetradecane,tridecane, C₈₋₂₀ isoparaffins, mineral oil, petrolatum, isoeicosane andpolyisobutene; C₁₀₋₃₀ cholesterol/lanosterol esters; lanolin; and thelike. Representative hydrocarbons include paraffinic hydrocarbonsavailable from Exxon under the ISOPARS trademark, and from the PermethylCorporation. In addition, C₈₋₂₀ paraffinic hydrocarbons such as C₁₂isoparaffin (isododecane) manufactured by the Permethyl Corporationhaving the tradename PERMETHYL 99 A™ are also contemplated to besuitable. Various commercially available C₁₆ isoparaffins, such asisohexadecane (having the tradename PERMETHYL®) are also suitable. Insome embodiments, silicone oils such as dimethicones, cyclic silicones,and polysiloxanes may also be included in the oil phase. In oneembodiment, silicone oils are present in an amount less than about 5% byweight of the oil phase.

In some embodiments, the composition and/or article includes thickeners.Examples of suspending and thickening agents include silica gels, gums,clays, fumed silica, fatty acid soaps, and various hydrocarbon gels, andother ingredients that when incorporated into the formulation remain onthe surface of keratinous tissues as disclosed in the InternationalCosmetic Dictionary and Handbook (12th Ed.), which is herebyincorporated by reference. In some embodiments, the composition and/orarticle includes viscosifying agents such as gellants. Examples ofviscosifying agents include bentone, triglycerides, aluminum stearate,C₁₈-C₃₆ acid glycol esters, glyceryl tribehenate, glycerol monostearate,alginates, carbomers, celluloses, gums, carageenans, starches orsilicates.

In some embodiments, the composition and/or article includes waxes.Examples of waxes include, but are not limited to, linear polyethylene,microcrystalline petroleum wax, carnauba wax, lignite wax, ouricouriwax, rice bran wax, castor wax, mortar wax, stearone, acrawax, bayberrywax, castor wax, Japan wax, ozokerite, beeswax, candelilla wax,petrolatum, ceresin wax, cocoa butter, illipe butter, esparto wax,shellac wax, ethylene glycol diesters or triesters of C₁₈-C₃₆ fattyacids, cetyl palmitate, paraffin wax, hard tallow, lanolin, lanolinalcohol, cetyl alcohol, glyceryl monostearate, sugarcane wax, jojobawax, stearyl alcohol, silicone waxes, and combinations thereof.

It is understood to those skilled in the art that any other cosmeticallyacceptable ingredients, i.e., those included in the CFTACosmeticIngredient Dictionary, 3rd Ed., may be used. Details on techniques forformulation and administration may be found in the latest edition of“Remington's Pharmaceutical Sciences” (Maack Publishing Co., Easton,Pa.).

Synthesis of Polymers (I), (II), and (III)

The novel polymers of the present disclosure can be prepared in avariety of ways known to one skilled in the art of organic synthesis.The polymers of the present disclosure can be synthesized using themethods as hereinafter described below, together with synthetic methodsknown in the art of synthetic organic chemistry or variations thereon asappreciated by those skilled in the art.

The polymers of this disclosure can be prepared from readily availablestarting materials using the following general methods and procedures.It will be appreciated that where typical or preferred processconditions (i.e., reaction temperatures, times, mole ratios ofreactants, solvents, pressures, etc.) are given; other processconditions can also be used unless otherwise stated. Optimum reactionconditions may vary with the particular reactants or solvent used, butsuch conditions can be determined by one skilled in the art by routineoptimization procedures.

The processes described herein can be monitored according to anysuitable method known in the art. For example, product formation can bemonitored by spectroscopic means, such as nuclear magnetic resonancespectroscopy (e.g., ¹H or ¹³C) infrared spectroscopy, spectrophotometry(e.g., UV-visible), or mass spectrometry, or by chromatography such ashigh performance liquid chromatography (HPLC) or thin layerchromatography.

Preparation of polymers can involve the protection and deprotection ofvarious chemical groups. The need for protection and deprotection, andthe selection of appropriate protecting groups can be readily determinedby one skilled in the art. The chemistry of protecting groups can befound, for example, in Greene, et al., Protective Groups in OrganicSynthesis, 4th. Ed., Wiley & Sons, 2006, which is incorporated herein byreference in its entirety.

The reactions of the processes described herein can be carried out insuitable solvents which can be readily selected by one of skill in theart of organic synthesis. Suitable solvents can be substantiallynonreactive with the starting materials (reactants), the intermediates,or products at the temperatures at which the reactions are carried out,i.e., temperatures which can range from the solvent's freezingtemperature to the solvent's boiling temperature. A given reaction canbe carried out in one solvent or a mixture of more than one solvent.Depending on the particular reaction step, suitable solvents for aparticular reaction step can be selected.

Resolution of racemic mixtures of compounds can be carried out by any ofnumerous methods known in the art. An example method includes fractionalrecrystallization using a “chiral resolving acid” which is an opticallyactive, salt-forming organic acid. Suitable resolving agents forfractional recrystallization methods are, for example, optically activeacids, such as the D and L forms of tartaric acid, diacetyltartaricacid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid orthe various optically active camphorsulfonic acids. Resolution ofracemic mixtures can also be carried out by elution on a column packedwith an optically active resolving agent (e.g.,dinitrobenzoylphenylglycine). Suitable elution solvent composition canbe determined by one skilled in the art.

The polymers of the disclosure can be prepared, for example, using thereaction pathways and techniques as described, for example, in Odian,George G. Principles of Polymerization, 4^(th) Ed., Hoboken, N.J.:Wiley-Interscience, 2004, herein incorporated by reference in itsentirety.

In some embodiments, the polymers of the present disclosure aresynthesized by starting with a multivalent polymer having amine terminalgroups. The amine terminal groups can be coupled to acrylic acidderivatives (e.g., acryloyl chloride, methacryloyl chloride, substitutedacryloyl chloride, acrylic acid, methacrylic acid, or substitutedacrylic acid) to form amide bonds. In some embodiments, the couplingreaction is performed under catalysis (e.g., base catalysis). In someembodiments, the acrylic acid derivatives are activated, for example,using N-hydroxysuccinimide. In some embodiments, the coupling reactionis performed in the presence of a coupling agent, such as a carbodiimideor the like.

In some embodiments, the polymer is incorporated into a compositionand/or article by mixing with any additional components of thecomposition and/or article using a mechanical mixer, high shear rotarymixer, a stirring mixer, a container shaker, and/or ultrasonicagitation.

To make an article formed entirely of the polymer, in some embodiments,the polymer is inserted into a mold, crosslinked in the mold by applyinga light and/or heat, and removed from the mold as a hydrogel.

To coat an article with the polymer, in some embodiments, a solutionincluding the polymer and one or more solvents is sprayed, painted, orotherwise applied to an article, or to a portion of an article. Thearticle is then dried to remove the solvents.

Methods of Use

This disclosure also features, inter alia, a method of using acomposition and/or article including a polymer of Formula (I), Formula(II), or Formula (III), including applying the composition and/orarticle to a skin portion; and exposing the skin portion to light and/orheat to provide a crosslinked polymer. In some embodiments, the lightand/or heat is generated by a device. In other embodiments, the lightand/or heat is provided by sunlight.

In some embodiments, to hydrate a skin portion, the composition and/orarticle including a polymer of Formulae (I), (II), or (III) is appliedto a skin portion, light and/or heat is then applied to crosslink thepolymer. In some embodiments, washing or scrubbing by hand and/or usingsonic cleansing devices removes the composition and/or article. Thecrosslinked polymer absorbs water to provide a film having a watercontent of 75% or more (e.g., 80% or more, 85% or more, 90% or more, or95% or more) by weight.

In some embodiments, the compositions and/or article (e.g., cosmeticcompositions) disclosed herein may be applied to one or more skinsurfaces and/or one or more mammalian keratinous tissue surfaces as partof a user's daily routine or regimen. In some embodiments, thecomposition and/or article is used on an “as needed” basis. In someexamples, an effective amount of the composition and/or article isapplied to a target portion of the keratinous tissue or skin.

In some embodiments, the method includes a step identifying a skinsurface for treatment with the composition and/or article for improvingskin condition. In some embodiments, the skin surface is identified bythe user or a third party such as a dermatologist, cosmetician, or otherindividual, or even by a combination of different individuals.Identification may be done, for example, by visual inspection of theskin surface in need of treatment.

In some embodiments, skin surfaces suitable for application of thecomposition and/or article include those not typically covered byclothing such as facial skin surfaces, hand and arm skin surfaces, footand leg skin surfaces, and neck and chest skin surfaces (e.g.,décolletage). For example, areas identified for application may includeareas such as the forehead, perioral, chin, periorbital, nose, and/orcheek skin surfaces. In another example, the composition and/or articleis applied to any facial skin care surface and/or any other skin surfaceidentified as in need of treatment by the composition and/or article.

In some embodiments, the method includes a step of applying thecomposition and/or article to the skin surface, which may or may nothave been previously identified. Many regimens exist for the applicationof the composition. In some embodiments, the composition and/or articleis applied as needed and/or at least once a day, twice a day, or on amore frequent daily basis. In some embodiments, the composition and/orarticle is applied over a period of, for example, between about 1 weekand about 12 weeks, between about 4 weeks and about 12 weeks, and/orbetween about 4 weeks and about 8 weeks, over multiple months (i.e.,3-12 months) or multiple years. In some embodiments, when applied twicedaily, the first and second applications are separated by at least 1 toabout 12 hours. For example, the composition (e.g., cosmeticcomposition) is applied in the morning and/or in the evening before bed.

In some embodiments, a composition and/or article including the polymeris delivered to a body portion once the polymer of Formulae (I), (II),or (III) has already been crosslinked. For example, in one embodiment, atissue scaffold containing a crosslinked polymer of Formulae (I), (II),or (III) is delivered a body portion to promote tissue growth. In someembodiments, the tissue scaffold is an implant, or is a portion of animplant. As another example, a drug-delivery composition and/or articleincluding a crosslinked polymer of Formulae (I), (II), or (III) and oneor more therapeutic agents is administered to a body portion anddelivers the therapeutic agents over a desired time period of, forexample, 1 day (e.g., 1 week, 2 weeks, 1 month, or 6 months) to 1 year(e.g., 6 months, 1 month, 2 weeks, or 1 week).

The following examples are provided to illustrate, not limit, thedisclosure.

EXAMPLES

Acrylamide systems have low toxicity and are suitable for applicationsin the cosmetic and/or pharmaceutical fields. Without wishing to bebound by theory, it is believed that anthraquinone-2-sulfonic acidsodium salt is relatively low in toxicity. For example, the HIMS ratingfor anthraquinone-2-sulfonic acid sodium salt is 1-health;0-flammability; 0-reactivity. Furthermore, anthraquinone-2-sulfonic acidsodium salt is water soluble and thus appropriate for hydrogelcrosslinking Its absorbance spectrum shows a n-π* transition from 385nm-440 nm but it is capable of generating a radical with light above 400nm. Several functionalized hydrogels were cured using this initiator asdiscussed below.

Example 1 Synthesis and Characterization of Acrylamide-terminatedOligo/Poly-ethylene Glycol

FIG. 1 illustrates the synthesis of a PEG polymer that is functionalizedby two acrylamide end groups. Referring to FIG. 1, poly(ethylene glycol)bis(amine) [1] (Aldrich, MW ˜2000, 1.0 g, 1 mmol NH₂ equivalents, LOT#MKBK4867V) was dissolved into 3.0 mL anhydrous chloroform in a threeneck 25 mL round bottom flask equipped with stir bar and drying tubefilled with anhydrous calcium chloride. To this solution was added 0.2 g(1.8 mmol) triethylamine [2] followed by 0.12 mL of acryloyl chloride[3] (1.5 mmol, Aldrich, LOT# SHBD4703V). The solution was allowed tostir for 3 hours and became a light yellow. The organic solvent andexcess acryloyl chloride were then rotary evaporated. The solids weredissolved into a 3:1 chloroform-hexanes mixture and eluted on silicagel. The solvents were rotary evaporated to yield 1.1 g of poly(ethyleneglycol) bis(acrylamide) [4] as a clear, colorless, odorless, viscousliquid. Proton NMR showed the ethyl ether protons of the PEG at 3.6 ppm.There were 40 repeat units which translates to approximately 160 ethylether protons. The acrylic protons are at 5.6 ppm, 6.1 ppm and at 6.4ppm while the amide proton is at 8.3 ppm.

The resulting poly(ethylene glycol) bis(acrylamide) was dissolved into 4mL of de-ionized water and ˜0.1 g of anthraquinone-2-sulfonic acidsodium salt (0.3 mmol, Aldrich, LOT# MKBG0884V). The solution was spreadover an acrylic block and exposed to blue illumination. The result was acured film of poly(ethylene glycol) bis(acrylamide) that was resistantto rinse at tap water pressure.

Example 2 Synthesis and Characterization of Acrylamide-terminatedTetravalent Poly(Ethylene Glycol)

Referring to FIG. 2, in a similar reaction setup as described in Example1, a 4-arm, amine terminated poly(ethylene oxide), [5] (Aldrich, MW˜10,000, 0.3 g, 0.12 mmol NH₂ equivalents) was dissolved into 2.5 mLanhydrous chloroform. To this solution was added 0.03 g (0.22 mmol)triethylamine [2] followed by 0.02 mL of acryloyl chloride [3] (0.2mmol, Aldrich, LOT# SHBD4703V). The solution was allowed to stir for 3hours under argon and remained colorless. The organic solvent and excessacryloyl chloride were then rotary evaporated. The solids were dissolvedinto a 3:1 chloroform-hexanes mixture and eluted on silica gel. Thesolvents were rotary evaporated to yield 0.3 g of poly(ethylene glycol)tetra(acrylamide) [6] as a clear, colorless, odorless, viscous liquid.

Example 3 Large-scale Synthesis and Characterization ofAcrylamide-terminated Jeffamine®

FIG. 3 illustrates the synthesis of acrylamide-terminated Jeffamine®[8A]-[8D]. the general synthetic procedure follows.

A 500.0 g quantity of Jeffamine ED-2003 (MW ˜1900, 0.53 mol amineequivalents, LOT#3F521) [7D] was added to 1000 mL water in a 3000 mLround bottom flask equipped with mechanical stirrer. After the Jeffaminedissolved, 45.0 g of potassium carbonate (0.33 mol) was added to theaqueous solution. The solution turned slightly cloudy and another 250 mLof water was added.

To 350 mL hexanes was added 58.8 g of acryloyl chloride (0.65 mol). Thehexanes solution was then transferred to an addition funnel. The hexanessolution was then added dropwise to the slowly stirring aqueous solutionof Jeffamine. The hexanes formed a layer on top of the water. Thebi-phasic reaction was allowed to continue for 12 hours and the solutionturned orange in color. The hexanes solution was then removed byseparatory funnel. The water was removed by rotary evaporation using anazeotrope with acetone and denatured alcohol. The solids were dissolvedinto denatured alcohol and the insoluble potassium salts were filteredoff. The denatured alcohol was then removed by rotary evaporation toyield an orange liquid final product [8D] which solidified when cooled.

The NMR of this product in DCCl₃ (below) showed carbamic acid(R—NH—C(═O)—OH) at 10.9 ppm, amide protons/HCCl3 at 7.2 ppm, acrylamideprotons at 5.9 to 6.2 ppm, Jeffamine ethyl ether protons at 3.6 ppm, andmethyl protons from the propylene oxide at 1.0 to 1.2 ppm. From the NMRit was determined that the Jeffamine ED-2003 consumed carbon dioxidefrom the potassium carbonate as it was formed. Thus, only ˜25% of theamine groups were converted to acrylamides while 75% of them wereconverted to carbamic acid moieties.

Example 4 Crosslinking of Acrylamide-functionalized Polyethylene Glycolin a Blend

A series of solutions was made to evaluate the crosslinking capabilitiesof blends of non-crosslinkable filler polymeric materials and theacrylamide-functionalized polyethylene glycol of Example 1. Thenon-crosslinkable polymeric material was dimethyl-terminatedpolyethylene glycol of 2 kDa molecular weight. The general procedureinvolved the dissolution of the acrylamide-functionalized PEG into waterin the ratios shown in Table 1, below. To the water solution was addedthe dimethyl terminated PEG followed by 0.5% anthraquinone-2-sulfonicacid sodium salt as the photo-initiator. The solutions were drawn downon an acrylic block and exposed to 365 nm light. All ratios formedfree-standing hydrogel films except for the lowest concentrationfunctionalized example (0.426 g PEG-acrylamide).

TABLE 1 Blend composition and film forming properties. PEG- RunAcrylamide PEG-Dimethyl Water Sucessful film 1 4.256 g 0 8.634 g Yes 23.598 g 3.426 g 9.045 g Yes 3 2.561 g 3.612 g 8.214 g Yes 4 1.236 g4.245 g 9.045 g Yes 5 0.868 g 4.097 g 8.847 g Yes 6 0.426 g 4.298 g8.839 g No

Example 5 Pigmented Photo-cured Hydrogel

Acrylamide terminated PEG (4.3 g) of Example 1 was dissolved intodeionized water (5.8 g). The polymer and water were well blendedtogether to provide a homogeneous mixture.

To this mixture was added 0.05 g of anthraquinone-2-sulfonic acid sodiumsalt as the photo-initiator. 2.3 g of mineral foundation (a mixture ofred, yellow, and black iron oxide and with white titania) was thenadded. The mixture was mixed at 1000 rpm using a small impeller bladefor 5 minutes. The mixture was drawn down on an acrylic sheet at athickness of 0.007″. This layer was exposed to a 400 nm light source for40 seconds and result was a free-standing pigmented hydrogel film.

While illustrative embodiments have been illustrated and described, itwill be appreciated that various changes can be made therein withoutdeparting from the spirit and scope of the disclosure.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:
 1. A polymer of Formula (I)

wherein: R¹, R², R³, and R⁶ are each independently selected from H andC₁₋₆ alkyl; R⁴ and R⁵ are each independently selected from H, C₁₋₆alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, and C₁₋₆ haloalkoxy; X is amultivalent linker selected from

 wherein R^(A) and R^(B) are each independently selected from H and C₁₋₆alkyl; L¹ is each independently —C₁₋₄ alkylene-O—; n is eachindependently an integer from 0 to 10,000, provided that the sum of alln in Formula (I) is not 0; and m is 2, 3, or
 4. 2. The polymer of claim1, wherein R¹, R², R³, and R⁶ are each independently selected from H andC₁₋₃ alkyl.
 3. The polymer of claim 1, wherein R¹, R², R³, and R⁶ areeach H.
 4. The polymer of claim 1, wherein X is a multivalent linkerselected from


5. The polymer of claim 1, wherein L¹ is each —CH₂O—.
 6. The polymer ofclaim 1, wherein n is each independently an integer of from 2 to 5,000.7. The polymer of claim 1, wherein m is
 2. 8. The polymer of claim 1,wherein m is
 4. 9. A compound, having Formula (IV)


10. The polymer of claim 1, wherein the polymer includes a dendrimer.11. The polymer of claim 1, wherein the polymer is crosslinkable in thepresence of a free-radical initiator and light.
 12. The polymer of claim11, wherein when the polymer is crosslinked, the polymer forms a film.13. The polymer of claim 11, wherein when the polymer is crosslinked,the polymer forms a hydrogel.
 14. The polymer of claim 13, wherein thehydrogel can absorb up to 50% by volume of water.
 15. A compositionincluding a polymer of claim 1 and a carrier.
 16. The composition ofclaim 15, wherein the composition is a cosmetic composition.
 17. Thecomposition of claim 15, wherein the composition is a pharmaceuticalcomposition.
 18. The composition of claim 15, further including atherapeutic agent.
 19. An article including a polymer of claim
 1. 20.The article of claim 19, wherein the article is a medical device. 21.The article of claim 19, wherein the article is selected from a bandage,a dressing, a tissue scaffold, a stent, an endoprosthesis, an implant, alens, and a medical film.